Novel non- cariogenic and non-caloric sweeteners for a variety of processed food and beverage products await future discoveries. Such sweeteners will have a dramatic impact on the marketplace and prevention of sugar- associated diseases, such as dental caries and diabetes. For patients with regulated dietary carbohydrate intake, the rationale for good- tasting synthetic sweeteners is obvious. This Phase I STTR Project will assess the ability of monoclonal antibodies made to sweet guanidines to screen combinatorial peptidomimetic libraries of compounds that may possess sweetener activity. The deployment of an antibody-based "Artificial Receptor" for the discovery of novel sweet compounds is unique to this project. The project has three milestones: (1) Develop biased combinatorial peptidomimetic libraries to identify novel ligands using monoclonal anti-sweetener antibodies: (2) Fluorescence polarization immunoassays to identify peptidomimetic ligands; (3) Generation of "second-iteration" biased libraries of candidate compounds for further characterization. Each Milestone will be carried out independently by the applicant organization or the research organization, however, the success of the project requires cooperation and partnership between both parties. The objective of this STTR proposal has high program relevance to the Caries, Nutrition and Fluoride Program of the National Institute of Dental Research (NIDR) and the mission of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE